Spinal Muscular Atrophy

Key Points:

  • Progressive muscle weakness
  • SMN gene mutation
  • Varying severity
  • Primary orthopaedic concerns: hip dislocations, scoliosis, and lower extremity contractures

Description:

Spinal muscle atrophy (SMA) involves a loss of alpha motor neurons in the anterior horn of the spine.  This leads to muscle weakness and atrophy.

Epidemiology:

SMA is the most common genetic disorder resulting in death during childhood.  It occurs in one out of 10,000 live births. 

Clinical Findings:

The primary finding is profound muscular weakness.  The deep tendon reflexes are absent.  The patient may have fasciculations, with tongue fasciculations being pathognomonic.  Scoliosis will usually be present at 2-3 years of age.

Imaging Studies:

Screening exams should include pelvis and spine radiographs.

Etiology:

Spinal muscle atrophy occurs as a result of a survival motor neuron (SMN) gene mutation which is present in 90% of patients with SMA.  All patients are lacking SMN-I protein.  The severity of disease is based on the number of functional SMN-II copies.

 

Treatment:

The primary affected musculoskeletal aspects of SMA, the hips, spine and lower extremities should be evaluated at each visit.  

Hips: Hips are commonly dislocated in SMA and reduction is controversial.  Many centers do not perform surgery to relocate because of the absence of motor function and that most patients are wheelchair ambulators, while others do, citing risk of late pain.     

Spine: Scoliosis is common in SMA and may present early.  Patients may be braced early with the goal of delaying surgery.  Growing instrumentation is a consideration for early onset patients.  Posterior spinal instrumentation and fusion should be performed to the pelvis in mature patients.

In December 2016, the FDA approved nusinersen (Spinraza), the first drug approved to treat children (including newborns) and adults with SMA. Nusinersen is anantisense oligonucleotide (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency.  As the delivery is intrathecal, any planned spinal fusion should allow for access to the intrathecal space via a “skip segment” of fusion.

The treatment of lower extremity contractures is controversial because of a high recurrence rate.  Also, surgical intervention rarely improves ambulation ability.

Complications:

Prognosis is varied by subtype. Nutritional deficiency and respiratory failure are problematic, with early mortality for type 1 SMA. Later onset is associated with milder symptoms and improved prognosis.  

Classification and Other Type Specific Features:

There are many different types of SMA.
  • Type I, acute Werdnig-Hoffman disease:  Presents at birth or a few months after.  These children are unable to support their head or sit independently.  There is a very poor prognosis and most children are deceased by 2 years of age.
  • Type II, chronic Werdnig-Hoffman disease:  Initial symptoms present at 6-12 months of age.  Muscle weakness is worse in the lower extremities.  About 60% of patients eventually have hip dislocations.  The patient’s may sit unsupported but typically do not ambulate.  Life expectancy for these patients is until the fifth decade.
  • Type III, Kugelberg-Welander disease: Presents between early childhood and adolescence.  Proximal weakness is the most common clinical finding.  The patients ambulate initially but progress to using wheelchairs as adults.  There is a normal life expectancy but occasionally respiratory support is required.
  • Type IV: Symptoms present after 30 years of age.  There is mild to moderate muscle weakness primarily affecting proximal musculature.
Types I-IV are all autosomal recessive.  X-linked SMA symptoms first appear in infancy.  These children often have joint contractures and they may have fractures at birth.

References:

NIH Genetics Home Reference: Spinal Muscular Atrophy http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Mesfin A, Sponseller PD, Leet AI. Spinal muscular atrophy: manifestations and management. J Am Acad Orthop Surg. 2012 Jun;20(6):393-401. 

Sucato DJ. Spine deformity in spinal muscular atrophy. J Bone Joint Surg Am. 2007 Feb;89 Suppl 1:148-54. Review. Erratum in: J Bone Joint Surg Am. 2007 May;89(5):1090-1

Top Contributors:

Dana Olszewski  MD,MPH